DESCRIPTION Diisocyanato compounds such as TDI, HDI, and MDI are considered to be an important cause of occupational asthma in the Western world. Molecular mechanisms by which these compounds exert their effect remain largely unknown. The research described in the application proposes to develop and apply sensitive biomarkers specific to diisocyanato-GSH adduction and to the oxidative stress evoked by adduct formation. Three specific aims are listed. These include (1) developing an analytical methodology for detection and quantitation of diisocyanato-GSH adducts in fluids and tissues, (2) studying mechanisms of oxidative stress that are caused by airborne levels of diisocyanates in cultured human lung cells, and (3) surveying the applicabilities of the quantitative measures of oxidative stress in blood samples obtained from humans exposed to known amounts of diisocyanates in controlled clinical settings.